Zenith™
Genomics for rare disease
Zenith™ genomics provides the most complete analysis for patients suspected of rare disease. Early testing is crucial to stop the diagnostic odyssey, guide early intervention, and provide families with the prognostic clarity they need.
Why genetic testing for rare disease?
When a child has complex health challenges—such as developmental delays, seizures, or a combination of healthcare issues—parents are often focused solely on managing the day-to-day needs of their child. However, treating individual symptoms without identifying the root cause leaves a critical gap in long-term care. The hidden toll of living without a clear diagnosis is significant, often leading to frequent ER visits and hospital stays.7
Genetic testing offers a pivotal opportunity to look deeper and find the single, foundational answer for these clinical issues. Moving genome sequencing to the front line not only improves a patient’s long-term quality of life but also helps reduce the emotional and financial burden of unnecessary medical interventions.
Collectively common, individually rare.
Rare diseases represent a global public health priority.
Worldwide
>350M
people around the world have a rare disease.1
Often Genetic
80%
of rare diseases are genetic.2
Underutilized
<10%
of kids with signs of genetic disease have had genetic testing.3
Major organizations now advocate for early, comprehensive genomic testing
Strongly recommends exome/genome sequencing be considered as a first- or second-tier test for patients with congenital anomalies, developmental delay or intellectual disability.4
Strongly recommends comprehensive genetic testing, like exome/genome sequencing, for all individuals with unexplained epilepsy, without limitation of age.5
Recommends exome/genome sequencing as a first-tier test for global developmental delay and intellectual disability in most circumstances because of superior diagnostic yield and higher cost-effectiveness if pursued earlier in the diagnostic process.6
Diagnostic Odyssey
Earlier genome sequencing improves quality of life and reduces healthcare costs
Patients can spend many years traveling to see multiple doctors and undertaking endless tests in their search for a diagnosis.
- It takes patients 4-7 years after symptoms begin to find the correct rare disease diagnosis.2
- On average, these patients see 7 different physicians for 17 appointments before a diagnosis is made.2
- This process can result in over $220,000 in avoidable medical expenses and lost family
income.7
Why choose ZenithTM genomics for your patients?
Our Zenith™ platform brings you the power of genome paired with advanced bioinformatics and long-read confirmatory sequencing to get you answers in one test. Guidelines and consensus statements recommend genome sequencing as a first tier test4-6, but as all tests are run on a PCR-free whole genome backbone, you can easily escalate between tests.
Delivering the comprehensive answers your patient needs right away and avoids the delays of iterative testing
Zenith™ Genome uses PCR-free whole-genome sequencing to evaluate protein coding and non-coding regions of the genome and includes copy number variant (CNV) analysis, mitochondrial genome analysis, and select tandem repeat expansion (TRE) analysis. The whole-genome backbone enables the ability to reanalyze a patient’s genome as new information becomes available.
- Confirmation of all reported variants and TREs by a secondary technology
- Comprehensive report including pathogenic variants, likely pathogenic variants, and variants of uncertain significance (VUS) correlated with the patient’s phenotype
- Option to receive ACMG-recommended secondary findings
- Complementary reanalysis every 12 months, starting one year after the initial report
Maximizing diagnostic yield by excelling at identifying variants often missed by standard exomes
Zenith™ Exome uses a PCR-free whole-genome backbone to evaluate protein coding regions of the genome, allowing enhanced coverage of exonic regions and higher resolution copy number variant (CNV) analysis compared to traditional exome sequencing. Mitochondrial genome analysis and select tandem repeat expansion (TRE) analysis are also included. The whole-genome backbone enables the ability to re-query a patient’s genome as new information becomes available and to seamlessly escalate to genome analysis.
- Confirmation of all reported variants and TREs by a secondary technology
- Comprehensive report including pathogenic variants, likely pathogenic variants, and variants of uncertain significance (VUS) correlated with the patient’s phenotype
- Option to receive ACMG-recommended secondary findings
- Complementary reanalysis every 12 months, starting one year after the initial report
Comprehensive primary screening comparable to chromosomal microarray with seamless escalation to exome or genome
Zenith™ copy number analysis (CNA) uses a PCR-free whole-genome backbone to detect genome-wide copy number variants (CNVs) with high coverage and resolution, producing indication-based results that include variants of the highest relevance to the patient’s phenotype. The whole-genome backbone enables the option to add Fragile X syndrome analysis to the initial order and/or re-requisition to exome or genome analysis.
- CNV report comparable to that of a CMA report
- Confirmation of all reported variants by a secondary technology
- Enhanced CNV detection7
- Comprehensive report including pathogenic variants, likely pathogenic variants, and variants of uncertain significance (VUS) correlated with the patient’s phenotype
- Option for FMR1 expansion analysis (Fragile X syndrome) add-on
FAQs
Who should have Zenith™ testing?
Zenith™ genetic testing is designed for individuals with clinical features suggestive of a genetic cause, including neurodevelopmental disorders like autism, developmental delays, and intellectual disability, as well as epilepsy and other congenital anomalies. When ordering Zenith™ exome or genome, it is recommended to include samples from both parents to improve interpretation.
Who can I contact if I have questions about which test to order or a patient result?
Board-certified genetic counselors are available to answer questions about Zenith™ CNA, exome or genome testing Monday through Friday, 6 AM to 5 PM Pacific Time, excluding holidays. Please email rarediseasegc@natera.com or call 650-249-9090 and ask for the “genetic counselor on call”.
Does Natera have genetic counselors, who can speak to my patients?
Yes, Natera provides a pre-test genetic information video for your patients and their parents, as well as a 15-minute live genetic information session with a board-certified genetic counselor to discuss Zenith™ testing results. Your patients can visit http://www.naterasession.com to schedule this session at a time that is convenient for them. Alternatively, patients can call 650-249-9090 to set up a complimentary genetic information session.
How do I begin offering Zenith™ testing in my practice?
You can contact Natera by calling 650-613-4688 or emailing raredisease@natera.com to speak to someone who can set up an account for you and walk you through the ordering process.
How do I order more kits?
You can order more kits in two ways:
- Tell your local clinical field specialist.
- Email raredisease@natera.com and tell them how many kits you want and where you would like them sent.
What are the sample requirements for Zenith™ testing?
Zenith™ requires two EDTA (purple-top) tubes of blood or 2 buccal swabs. Collected samples should be shipped to Natera on the same day as the sample acquisition.
What does a Zenith™ CNA report look like?
Click here to view a Zenith™ CNA sample report.
What does a Zenith™ exome report look like?
Click here to view a Zenith™ exome sample report.
What does a Zenith™ genome report look like?
Click here to view a Zenith™ genome sample report.
How are variants classified and reported?
Zenith™ reports follow the joint ACMG/AMP guidelines, ensuring clinical decisions are based on a rigorous, standardized classification system.
- Comprehensive Reporting: Reports include Pathogenic (P), Likely Pathogenic (LP), and Variants of Uncertain Significance (VUS).
- Phenotypic Correlation: Variants are strictly filtered and prioritized based on the patient’s specific clinical indications and symptoms provided at the time of order.
- Secondary Findings: Consistent with ACMG recommendations, secondary findings in medically actionable genes are included in a separate report, unless the patient/clinician have opted out of these.
What are the typical turnaround times for primary and upgraded analysis?
- Primary Results: Most initial Zenith™ results (CNA, exome, or genome) are delivered within 6-8 weeks of the day all samples are received.
- Re-requisition/Upgrades: Because the data already exists on the whole-genome backbone, upgrades to exome or genome analysis are typically completed in just 3 weeks.
Is Zenith™ right for your patients?
We’re here to help you decide
1Global Genes. RARE Disease Facts. Web. Accessed March 21, 2025. https://globalgenes.org/rare-disease-facts/.
2Yang G, Cintina I, Zhou M, et al. The National Economic Burden of Rare Disease Study. The EveryLife Foundation for Rare Diseases. Published February 25, 2021. https://everylifefoundation.org/wp-content/uploads/2021/02/The_National_Economic_Burden_of_Rare_Disease_Study_Summary_Report_February_2021.pdf.
3Schroeder BE, Gonzaludo N, Everson K, Than KS, Sullivan J, Taft RJ, Belmont JW. The diagnostic trajectory of infants and children with clinical features of genetic disease. NPJ Genomic Medicine. 2021 Nov 22;6(1):98. DOI: 10.1038/s41525-021-00260-2.
4Manickam K, McClain MR, Demmer LA, et al. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine. 2021;23:2029–2037. DOI: 10.1038/s41436-021-01242-6.
5Smith L, Malinowski J, Ceulemans S, Peck K, Walton N, Sheidley BR, Lippa N. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. Journal of Genetic Counseling. 2023;32:266–280. DOI: 10.1002/jgc4.1646.
6Rodan LH, Stoler J, Chen E, Geleske T; Council on Genetics. Genetic evaluation of the child with intellectual disability or global developmental delay: Clinical report. Pediatrics. 2025 Jul;156(1):e2025072219. DOI: 10.1542/peds.2025-072219.
7Meienberg J, et al. Clinical sequencing: is WGS the better WES?. Human Genetics. 2016;135:359–362.